A tridimensional atlas of the developing human head.

The evolution and development of the head have long captivated researchers due to the crucial role of the head as the gateway for sensory stimuli and the intricate structural complexity of the head. Although significant progress has been made in understanding head development in various vertebrate species, our knowledge of early human head ontogeny remains limited. Here, we used advanced whole-mount immunostaining and 3D imaging techniques to generate a comprehensive 3D cellular atlas of human head embryogenesis. We present detailed developmental series of diverse head tissues and cell types, including muscles, vasculature, cartilage, peripheral nerves, and exocrine glands. These datasets, accessible through a dedicated web interface, provide insights into human embryogenesis. We offer perspectives on the branching morphogenesis of human exocrine glands and unknown features of the development of neurovascular and skeletomuscular structures. These insights into human embryology have important implications for understanding craniofacial defects and neurological disorders and advancing diagnostic and therapeutic strategies.

A 3D atlas of the human developing pancreas to explore progenitor proliferation and differentiation.

AIMS/HYPOTHESIS: Rodent pancreas development has been described in great detail. On the other hand, there are still gaps in our understanding of the developmental trajectories of pancreatic cells during human ontogenesis. Here, our aim was to map the spatial and chronological dynamics of human pancreatic cell differentiation and proliferation by using 3D imaging of cleared human embryonic and fetal pancreases. METHODS: We combined tissue clearing with light-sheet fluorescence imaging in human embryonic and fetal pancreases during the first trimester of pregnancy. In addition, we validated an explant culture system enabling in vitro proliferation of pancreatic progenitors to determine the mitogenic effect of candidate molecules. RESULTS: We detected the first insulin-positive cells as early as five post-conceptional weeks, two weeks earlier than previously observed. We observed few insulin-positive clusters at five post-conceptional weeks (mean ± SD 9.25±5.65) with a sharp increase to 11 post-conceptional weeks (4307±152.34). We identified a central niche as the location of onset of the earliest insulin cell production and detected extra-pancreatic loci within the adjacent developing gut. Conversely, proliferating pancreatic progenitors were located in the periphery of the epithelium, suggesting the existence of two separated pancreatic niches for differentiation and proliferation. Additionally, we observed that the proliferation ratio of progenitors ranged between 20% and 30%, while for insulin-positive cells it was 1%. We next unveiled a mitogenic effect of the platelet-derived growth factor AA isoform (PDGFAA) in progenitors acting through the pancreatic mesenchyme by increasing threefold the number of proliferating progenitors. CONCLUSIONS/INTERPRETATION: This work presents a first 3D atlas of the human developing pancreas, charting both endocrine and proliferating cells across early development.

Prevalence and Correlates of Food Insecurity Among Older Adults in the United States.

This study analyzed the 2021 National Health Interview Survey (NHIS) to assess food insecurity among adults aged 65 and older. Among 8,877 older adults, 4 percent (N=287) reported low or very low food security levels. Those who identified as Black or African American and Hispanic or Latino were more likely to experience food insecurity compared to White individuals. The study found that merely surpassing the poverty threshold might not be sufficient to protect against food insecurity. It also underscored socioemotional support's protective role in older adults' food security. Social workers must recognize various factors influencing food security among older adults.

Prevalence of hyponatremia and associated factors in patients with chronic kidney disease: the Fukuoka Kidney Disease Registry (FKR) study.

BACKGROUND: Hyponatremia is a common and important electrolyte disorder. However, the prevalence and factors associated with hyponatremia in patients with chronic kidney disease (CKD) are unknown. METHODS: We studied the factors associated with hyponatremia (< 135 mEq/L) in CKD patients registered in the Fukuoka Kidney Disease Registry (FKR) study using a logistic regression model variable selected using the variable reduction method. RESULTS: We analyzed the baseline characteristics of 4367 participants with CKD (age, 64 ± 16 years; male, 56.1%). Hyponatremia was detected in 2.0% of the patients at baseline, and multivariate logistic analysis showed that the independent factors for hyponatremia were body mass index (odds ratio [OR] 0.91; 95% confidence interval [CI] 0.85-0.97), prescription of benzodiazepine (OR 2.31; 95% CI 1.39-3.86), blood hemoglobin level (OR 0.76; 95% CI 0.65-0.88), and serum C-reactive protein level (OR 1.27; 95% CI 1.04-1.54). CONCLUSION: The cross-sectional analysis using baseline data from the FKR study revealed independent factors associated with hyponatremia in patients with decreased kidney function. Longitudinal analyses of the FKR cohort are needed to evaluate the effects of these factors on the prognosis of hyponatremia in patients with CKD.

Strategies for implementing music-based interventions for people with dementia in long-term care facilities: A systematic review.

OBJECTIVES: Research has found that music-based interventions can decrease behavioral and psychological symptoms of dementia or behaviors that challenge (BPSD/BtC). However, how to effectively implement these interventions is unclear. This study synthesizes available evidence regarding implementation strategies and outcomes of music-based interventions for people with dementia at residential long-term care facilities. METHODS: Study registered with PROSPERO (registration number: CRD42020194354). We searched the following databases: PsychInfo, PubMed, MEDLINE, CINAHL, and The Cochrane Library. Inclusion criteria included articles targeting music-based interventions conducted for people with dementia, studies conducted in residential long-term care facilities, and articles that reported implementation strategies and outcomes of the intervention. RESULTS: Of the included eight studies, half were studies of music therapy and the other half were on individualized music. 49 implementation strategies were reported. The most frequently reported category of strategies was planning (34.7%), followed by education (24.5%), quality management (24.5%), restructuring (12.2%), and finance (4.1%). No strategies under the category of attending to the policy context were reported. The most frequently reported implementation outcomes were appropriateness (27.3%), followed by adoption (22.7%), fidelity (22.7%), acceptability (9.1%), sustainability (9.1%), and cost (9.1%). No studies measured feasibility or penetration. CONCLUSIONS: Although various effective implementation strategies were identified, we were unable to examine the effectiveness of individual implementation strategies due to the designs of the selected studies. Less attention has been paid to strategies that aim at structural changes of intervention delivery systems. Future studies should investigate facilitators and barriers of implementing music-based interventions especially focusing on structural aspects.

Advance care planning in medicare/medicaid-funded agencies: providing a training in cultural competence.

This study presents a training that was developed for staff members at Medicare/Medicaid agencies to improve their knowledge and comfort levels in working on advance care planning (ACP) with their clients in a culturally competent manner. The training was developed to address the need to clarify the different types and purposes of ACP and to help develop the skills needed to work with clients of diverse cultural backgrounds. The evaluation of findings from the training showed the positive impacts that it had on participants; in particular, they exhibited demonstrated improvement in their knowledge of and comfort levels with ACP. The participants also expressed interest in receiving continued training surrounding ACP to increase their cultural competency skills and to receive updated information on ACP policies and practices.

Culturally Responsive Companion Program for a Japanese Woman with Dementia in a U.S. Nursing Home.

The older foreign-born population is predicted to increase in the United States. As a whole, this population in the long-term care setting is more likely to face greater challenges associated with loneliness and social isolation due to their smaller social networks, language and cultural differences. The benefits of person-centered care have been widely recognized and may be a potential remedy for such challenges felt by older immigrants. Using a qualitative case study approach, this study explored the staff perceptions of a culturally responsive companion program provided to an older Japanese woman with advanced dementia in the long-term care setting to understand the potential benefits of such a program. The first theme that emerged was that the client benefitted from the program in regard to her physical wellbeing, emotional wellbeing, language communication and cultural support. Given the support of Japanese companions, the client was able to express her needs and health symptoms effectively and the staff were subsequently able to provide culturally-sensitive care. The second theme that emerged was the perceived benefits received by the staff. The companion program improved the staff's ability to provide quality care for the resident. This study implies that culturally responsive companion programs may benefit foreign-born older individuals in improving their wellbeing in long-term care settings.

A web-based training program for direct care workers in long-term care communities: Providing knowledge and skills to implement a music and memory intervention.

As dementia increases and the availability of at-home caregivers decreases, the need grows for effective training for direct care workers. Direct care workers have demanding schedules with restrictive availability and lack professional incentives to pursue specialized training. This study explored the impact of the Mason Music & Memory Initiative (M3I), a web-based, micro-learning training for direct care workers, combined with the implementation of the Music & Memory intervention. The training provided a foundational understanding of dementia and the person-centered music intervention. Twenty-five direct care workers, across two long-term care communities, completed the training modules over four weeks. All participants completed a pre- and posttest, determining their knowledge and understanding of dementia and the Music & Memory intervention adopted by their facilities. Many workers found the training to be informative and inspiring, noting improved behaviors in residents during the implementation of the M3I.

Epithelial Lining Fluid and Plasma Concentrations of Dalbavancin in Healthy Adults after a Single 1,500-Milligram Infusion.

Dalbavancin is a lipoglycopeptide antibiotic with a prolonged half-life. A phase 1 study assessed dalbavancin levels in epithelial lining fluid (ELF) in 35 healthy adults using ELF bronchial microsampling up to 168 h after administration of 1,500 mg dalbavancin. The penetration of dalbavancin into ELF was 36%. ELF levels of dalbavancin exceeded the MIC90s of Streptococcus pneumoniae and Staphylococcus aureus for ≥7 days.

Rapid identification of genes controlling virulence and immunity in malaria parasites.

Identifying the genetic determinants of phenotypes that impact disease severity is of fundamental importance for the design of new interventions against malaria. Here we present a rapid genome-wide approach capable of identifying multiple genetic drivers of medically relevant phenotypes within malaria parasites via a single experiment at single gene or allele resolution. In a proof of principle study, we found that a previously undescribed single nucleotide polymorphism in the binding domain of the erythrocyte binding like protein (EBL) conferred a dramatic change in red blood cell invasion in mutant rodent malaria parasites Plasmodium yoelii. In the same experiment, we implicated merozoite surface protein 1 (MSP1) and other polymorphic proteins, as the major targets of strain-specific immunity. Using allelic replacement, we provide functional validation of the substitution in the EBL gene controlling the growth rate in the blood stages of the parasites.

Increased Serum Levels of α-Synuclein in Patients With Major Depressive Disorder.

OBJECTIVE: Epidemiologic studies have demonstrated that depression is a risk factor for dementia. In particular, dementia with Lewy bodies (DLB) has been noted to be highly relevant to depression. It has been suggested that α-synuclein (α-syn), a major component of Lewy bodies, is related to the onset and progression of DLB. To investigate the relationship between depression and DLB, we compared serum α-syn levels of patients with depression to those of healthy subjects. METHODS: The subjects were 103 inpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), or DSM-5 major depressive disorder (MDD) and 132 healthy comparisons. Patients were recruited from Juntendo Koshigaya Hospital, Saitama, Japan, between June 2010 and November 2016. Serum α-syn levels were measured using an enzyme-linked immunosorbent assay kit. Serum α-syn levels were compared using a 2 (age group [<60 years versus ≥60 years]) × 2 (diagnosis [MDD versus comparison]) analysis of variance. RESULTS: There was no significant main effect of age (F = 1.167, df = 1, 231, p = 0.281). There was a significant main effect of diagnosis (F = 44.657, df = 1, 231, p <0.001), with higher α-syn levels in the MDD group versus the healthy comparison group, regardless of age. CONCLUSION: The present results suggest that depression may affect the metabolism of α-syn; there is a possibility that depression is not only a prodromal symptom of DLB but also a causal risk factor for DLB.

Effect of a single dose of insulin glargine/lixisenatide fixed ratio combination (iGlarLixi) on postprandial glucodynamic response in Japanese patients with type 2 diabetes mellitus: A phase I randomized trial.

This report describes novel clinical data assessing the pharmacodynamics of insulin glargine/lixisenatide (iGlarLixi) compared with placebo and insulin glargine alone, to determine pharmacokinetics of lixisenatide, and to assess safety of iGlarLixi in Japanese people with type 2 diabetes mellitus (T2DM). In a single-centre, open-label, randomized, placebo-controlled cross-over study, participants received subcutaneous iGlarLixi 5 U/5 µg and 10 U/10 µg, placebo, and 5 U insulin glargine. The primary endpoint was area under the postprandial plasma glucose (PPG) curve (AUC0-2h ). A total of 20 participants completed all study periods. iGlarLixi 5 U/5 µg and 10 U/10 µg reduced mean PPG dose-dependently compared with placebo and insulin glargine 5 U. Both combinations significantly reduced PPG-AUC0-2h dose-dependently compared with placebo (least squares mean difference -7.48 mmol h/L for 5 U/5 µg, -10.75 mmol h/L for 10 U/10 µg; P < 0.0001). iGlarLixi 5 U/5 µg reduced PPG-AUC0-2h significantly compared with insulin glargine 5 U (-0.76 mmol h/L; P < 0.0001). No symptomatic hypoglycaemia occurred during the study. iGlarLixi single subcutaneous injections significantly and dose-dependently reduced PPG compared to placebo or insulin glargine in Japanese participants with T2DM. iGlarLixi was safe and well tolerated, and would be expected to provide the 24-hour plasma glucose-lowering effects of insulin glargine and the postprandial antihyperglycaemic effects of lixisenatide.

Safety of live attenuated varicella-zoster vaccine in patients with underlying illnesses compared with healthy adults: a prospective cohort study.

BACKGROUND: In Japan, freeze-dried live attenuated varicella-zoster vaccine is available for adults aged ≥50 years to prevent herpes zoster. However, limited evidence has been accumulated regarding vaccine safety for patients with underlying illnesses, who have been considered as the high-risk group for herpes zoster. METHODS: A prospective cohort study of 1200 healthy adults and 300 patients with underlying illnesses such as malignancy, diabetes mellitus, autoimmune diseases, and renal diseases was conducted. All subjects were vaccinated and then their adverse events (AEs) were followed for 28 days after vaccination. Key safety measures included any AEs, severe AEs (SAEs), and vaccine-related AEs such as injection-site AEs and systemic AEs. The frequencies and 95% confidence intervals of AEs were calculated. RESULTS: During the follow-up period, 2 SAEs (bone fracture and acute cholecystitis) among healthy adults and 1 SAE (disseminated mycobacteriosis) among patients with underlying illnesses were reported, although none of them was diagnosed as vaccine-related. Vaccine-related AEs were reported in 42% of healthy adults and patients with underlying illnesses, and the proportions were similar between the groups. The most frequent AEs were injection-site AEs in both groups (i.e., 41 and 39%), and systemic AEs were observed in 4% of both groups. Only among healthy adults, those with a history of herpes zoster were more likely to report injection-site AEs than those without a history of herpes zoster (53% vs 39%). CONCLUSIONS: The present study confirmed the safety of freeze-dried, live attenuated varicella-zoster vaccine even in patients with underlying illnesses. A history of herpes zoster might be related to development of injection-site AEs in healthy adults. TRIAL REGISTRATION: The study was prospectively registered on Japic-Clinical Trials Information as JapicCTI-163415 on October 31, 2016.

Consolidated Measures of Activity among Older Adults: Results of a Three Data Set Comparison.

This study explores the potential to consolidate a broad range of activity items to create more manageable measures that could be used in statistical modeling of multi-activity engagement. We utilized three datasets in the United States: Panel Study of Income Dynamics, Health and Retirement Study, and Midlife in the United States. After identifying activity items, exploratory and confirmatory factor analysis were used to empirically explore composite activity measures. Findings suggest that discrete activity items can be consolidated into activity domains; however, activity domains differ across datasets depending on availability of activity items. Implications for research and practice are further discussed.

"I'm just trying to cope for both of us": Challenges and supports of family caregivers in participant-directed programs.

Recently, national attention has focused on the needs of family caregivers providing complex chronic care, noting the necessity to better understand the scope of challenges they encounter. Although a robust body of literature exists about the scope of family caregiving, little is known specifically about the experiences and perspectives of family caregivers who support participant directed (PD) participants, particularly across the caregiving trajectory. Therefore, the aim of this qualitative descriptive study was to describe what family caregivers of individuals with developmental disabilities, physical disabilities, aging, or chronic health conditions identify as the challenges they experience as complex, and their perceptions of the effectiveness and gaps in family support resources in PD. Semi-structured interviews were audio-recorded with a purposive sample of caregivers. Transcribed interviews were analyzed using conventional content analysis. Fifty-four caregivers of individuals with a range of disabilities participated (age 34-78, M 59.9 ± 8.8; male 19%; spouse 17%, parent 61%). Six categories emerged from the analysis: contextualizing complexity, complexity in transitions, coping with complexity: advocacy & isolation, supportive support, unsupportive support, and systems challenges. Caregivers emphasized the interplay between unpredictability, transitions, and complexity and the interaction between the person receiving support, the caregiver's own situation, and the environment. Findings highlight the need, and provide a guide, for family assessment and for tailoring interventions matched to the profiles and self-identified challenges of families living with disability. Social workers can learn what families see as complex and what support broker behaviors families find helpful, and which not.

Advance Directives Information Delivery in Medicare/Medicaid-Funded Agencies: An Exploratory Study.

To encourage citizens to plan their end-of-life care to protect their autonomy, Congress passed the Patient Self-Determination Act (PSDA) in 1990. Under the PSDA, all Medicare/Medicaid-funded agencies are required to ask if all the patients, upon admission, have advance directives (ADs). If they have not formulated an AD, agencies need to inform that they have a right to do so and provide them with the written information. Although this is required by law, there is no universal procedure or set standard approach to deliver the information to patients in these agencies. It is often unclear who provides and explains information on ADs, and what materials are provided. The purpose of this study was to understand the procedures and challenges presented in the delivery of information about ADs in agencies in response to the PSDA requirements. Using a case study approach, semi-structured interviews with personnel in nine agencies were analyzed and three overarching themes were identified: organizational procedures, staff interactions, and staff perceptions. The findings indicated that there is a need for AD-specific training for staff responsible for delivering AD information to their clients. Implementation of a formalized procedure/guidelines for information delivery would be helpful to maintain quality standards across agencies.

Within-host competition does not select for virulence in malaria parasites; studies with Plasmodium yoelii.

In endemic areas with high transmission intensities, malaria infections are very often composed of multiple genetically distinct strains of malaria parasites. It has been hypothesised that this leads to intra-host competition, in which parasite strains compete for resources such as space and nutrients. This competition may have repercussions for the host, the parasite, and the vector in terms of disease severity, vector fitness, and parasite transmission potential and fitness. It has also been argued that within-host competition could lead to selection for more virulent parasites. Here we use the rodent malaria parasite Plasmodium yoelii to assess the consequences of mixed strain infections on disease severity and parasite fitness. Three isogenic strains with dramatically different growth rates (and hence virulence) were maintained in mice in single infections or in mixed strain infections with a genetically distinct strain. We compared the virulence (defined as harm to the mammalian host) of mixed strain infections with that of single infections, and assessed whether competition impacted on parasite fitness, assessed by transmission potential. We found that mixed infections were associated with a higher degree of disease severity and a prolonged infection time. In the mixed infections, the strain with the slower growth rate was often responsible for the competitive exclusion of the faster growing strain, presumably through host immune-mediated mechanisms. Importantly, and in contrast to previous work conducted with Plasmodium chabaudi, we found no correlation between parasite virulence and transmission potential to mosquitoes, suggesting that within-host competition would not drive the evolution of parasite virulence in P. yoelii.

Serum Levels of Albumin-ß-Amyloid Complex in Patients with Depression.

OBJECTIVE: Epidemiologic studies have demonstrated that suffering from depression may be a risk for Alzheimer disease (AD). As a possible biologic mechanism underlying the transition from depression to AD, it has been speculated that pathologic changes in ß-amyloid (Aß) metabolism are involved. To further understand the peripheral kinetics of amyloid in patients with depression, we investigated serum levels of free Aß and albumin-bound Aß. METHODS: Seventy inpatients with DSM-IV major depressive disorder (MDD) and 81 healthy individuals (the comparison group) were recruited between June 2012 and February 2014. Serum Aß40 and Aß42 levels, Aß40/Aß42 ratio, and serum levels of albumin-Aß complexes (SLAACs) were compared between the comparison group and patients in two age groups comprising younger (<60 years) and elderly (≥60 years) people. RESULTS: SLAAC was decreased in older patients with MDD but not in younger patients. The serum-free Aß40/Aß42 ratio was higher in patients with depression, even in younger patients. CONCLUSION: Our findings suggest that free Aß and the albumin-bound Aß reflect a different serum amyloid kinetics in depression. We speculate that serum-free Aß reflects changes in amyloid metabolism in patients suffering from depression and albumin-bound Aß reflects AD pathology and may be a potential predictor of the prodromal stage of AD.

The Influence of Sociodemographic and Psychosocial Factors on Advance Care Planning.

This study investigated sociodemographic and psychosocial factors that enhance or impede the completion of advance care planning, analyzing data from the Health and Retirement Study. The analytic subsample included the panel participants who died between 2006 and 2010 and who had answered the psychosocial and lifestyle questionnaire when they were alive. Multinomial logistic regression was executed to answer the research question (N = 1,056). The study found that persons who were older, who were women, who identified themselves as White, and who had higher levels of income and education were more likely to be motivated to complete advance care planning. Having greater sense of control was found to weaken the adverse relationship between being African American and the completion of advance directives. Having cancer, suffering from the illnesses for longer periods of time, and having experience of nursing home institutionalization also predicted the completion of advance care planning. Implications include incorporating a culturally tailored approach for racial/ethnic minorities and using advance directives that are clear and easily understood. In addition, future research needs to include a larger minority population and examine the extent to which variations between racial/ethnic groups exist in relation to advance care planning.

[Development of a Crisis Management Manual for Occupational Health Experts].

When crises such as natural disasters or industrial accidents occur in workplaces, not only the workers who are injured, but also those who engage in emergency or recovery work may be exposed to various health hazards. We developed a manual to enable occupational health (OH) experts to prevent health hazards. The manual includes detailed explanations of the characteristics and necessary actions for each need in the list of "OH Needs During Crisis Management" developed after an analysis of eight cases in our previous research. We changed the endings of explanatory sentences so that users could learn how often each need occurred in these eight cases. We evaluated the validity of the manual using two processes: 1) Providing the manual to OH physicians during an industrial accident; 2) Asking crisis management experts to review the manual. We made improvements based on their feedback and completed the manual. The manual includes explanations about 99 OH needs, and users can learn how and what to do for each need during various crisis cases. Because additional OH needs may occur in other crises, it is necessary to collect information about new cases and to improve the comprehensiveness of the manual continuously. It is critical that this crisis management manual be available when a crisis occurs. We need to inform potential users of the manual through various media, as well as by posting it on our website.